Inherited proximal tubular disorders and nephrolithiasis

Oliveira, Ben; Unwin, Robert J.; Walsh, Stephen B.

doi:10.1007/s00240-018-01103-z

Cited by 8 publications

(6 citation statements)

References 67 publications

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“…Calcium oxalate monohydrate stones are the most common type of kidney stones [24]. In addition, oxalate is the most important factor in the accumulation of urinary liquid crystals and is also an important cause of proximal and distal kidney tubular cell damage [8][9][10]. Therefore, studying the toxic effect of oxalate on renal tubular epithelial cells is vitally important to determine the mechanism of kidney stone formation.…”

Section: Discussionmentioning

confidence: 99%

“…Damage to renal tubular epithelial cells and the supersaturation of crystals in urine are the two major foundations for the formation of kidney stones [6,7]. High concentrations of oxalate can cause damage to proximal and distal kidney tubular cells, and oxalate is also the most important factor in crystal aggregation [8][9][10]. Autophagy is a highly conserved process used to degrade and recycle biological macromolecules or damaged organelles and is involved in a variety of human diseases [11].…”

Section: Introductionmentioning

confidence: 99%

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Oxalate Activates Autophagy to Induce Ferroptosis of Renal Tubular Epithelial Cells and Participates in the Formation of Kidney Stones

Song

Liao

Chen

et al. 2021

Oxidative Medicine and Cellular Longevity

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Renal tubular epithelial cell damage is the basis for the formation of kidney stones. Oxalate can induce human proximal tubular (HK-2) cells to undergo autophagy and ferroptosis. The present study was aimed at investigating whether the ferroptosis of HK-2 cells induced by oxalate is caused by the excessive activation of autophagy. We treated HK-2 cells with 2 mmol/L of oxalate to establish a kidney stone model. First, we tested the degree of oxidative damage and the level of autophagy and ferroptosis in the control group and the oxalate intervention group. We then knocked down and overexpressed the BECN1 gene and knocked down the NCOA4 gene in HK-2 cells, followed by redetection of the above indicators. We confirmed that oxalate could induce autophagy and ferroptosis in HK-2 cells. Moreover, after oxalate treatment, overexpression of the BENC1 gene increased cell oxidative damage and ferroptosis. In addition, knockdown of NCOA4 reversed the effect of oxalate-induced ferroptosis in HK-2 cells. Our results show that the effects of oxalate on the ferroptosis of HK-2 cells are caused by the activation of autophagy, and knockdown of the NCOA4 could ameliorate this effect.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Oxalate Activates Autophagy to Induce Ferroptosis of Renal Tubular Epithelial Cells and Participates in the Formation of Kidney Stones

Song

Liao

Chen

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…distal renal tubular acidosis (dRTA) is rooted in mutations in SLC4A1 [ 68 ]. The dominant pseudohypoaldosteronism type 1 (PHA1) is associated with NR3C3 mutations whilst recessive refers to SCNN1A , 1B and 1G [ 69 ]. Magnesium transporters are also subjected to genetic diseases, such as Bartter syndrome and its variant, Gitelman syndrome.…”

Section: Genetic Kidney Diseasesmentioning

confidence: 99%

“…Another important function of the PT is the activation of vitamin D, important for the reabsorption of calcium [ 69 ]. This PT feature has been replicated in a KOC model that showed levels of vitamin D metabolism similar to in vivo, suggesting that these models can improve the maturity and function of PT cells when compared to 2D monolayer cultures [ 70 ].…”

Section: Kidney Genetic Diseases-on-chipmentioning

confidence: 99%

Organs-on-chip technology: a tool to tackle genetic kidney diseases

et al. 2022

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Chronic kidney disease (CKD) is a major healthcare burden that takes a toll on the quality of life of many patients. Emerging evidence indicates that a substantial proportion of these patients carry a genetic defect that contributes to their disease. Any effort to reduce the percentage of patients with a diagnosis of nephropathy heading towards kidney replacement therapies should therefore be encouraged. Besides early genetic screenings and registries, in vitro systems that mimic the complexity and pathophysiological aspects of the disease could advance the screening for targeted and personalized therapies. In this regard, the use of patient-derived cell lines, as well as the generation of disease-specific cell lines via gene editing and stem cell technologies, have significantly improved our understanding of the molecular mechanisms underlying inherited kidney diseases. Furthermore, organs-on-chip technology holds great potential as it can emulate tissue and organ functions that are not found in other, more simple, in vitro models. The personalized nature of the chips, together with physiologically relevant read-outs, provide new opportunities for patient-specific assessment, as well as personalized strategies for treatment. In this review, we summarize the major kidney-on-chip (KOC) configurations and present the most recent studies on the in vitro representation of genetic kidney diseases using KOC-driven strategies.

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“…Now, we have a more detailed knowledge of the abnormalities in the proximal and distal nephron that cause stone formation and of their frequently monogenic origin. The articles by Oliveira et al [10] and Fuster et al [11] cover these topics, together with the comprehensive overview by Vezzoli et al on the relationship between kidney stone disease and the calcium-sensing receptor [12]. For many disorders, our more in-depth knowledge has yet to generate targeted therapies, but the two articles on the primary hyperoxalurias [13,14] paint an encouraging picture for the diagnosis and treatment of these very rare, severe disorders.…”

mentioning

confidence: 99%

Empirical therapy or precision medicine for kidney stone formers in the ‘-omics’ era?

Gambaro

2018

Urolithiasis

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Inherited proximal tubular disorders and nephrolithiasis

Cited by 8 publications

References 67 publications

Oxalate Activates Autophagy to Induce Ferroptosis of Renal Tubular Epithelial Cells and Participates in the Formation of Kidney Stones

Oxalate Activates Autophagy to Induce Ferroptosis of Renal Tubular Epithelial Cells and Participates in the Formation of Kidney Stones

Organs-on-chip technology: a tool to tackle genetic kidney diseases

Empirical therapy or precision medicine for kidney stone formers in the ‘-omics’ era?

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